MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily
MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily
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DOI：
10.1073/pnas.94.21.11514
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发表时间：
1997-10-14
影响因子：
11.1
通讯作者：
Breit, SN
中科院分区：
文献类型：
--
作者：
Bootcov, MR;Bauskin, AR;Breit, SN
巨噬细胞在涉及免疫和炎症反应的正常和病理过程中发挥关键作用，在很大程度上是通过它们分泌广泛的生物活性分子的能力。为了鉴定这些尚未表征的分子中的一些，我们使用了设计用于鉴定与巨噬细胞活化相关表达的基因的消减克隆方法，这些基因之一，命名为巨噬细胞抑制性细胞因子1（MIC-1），编码具有转化生长因子β的结构特征的蛋白质（TGF-β）超家族细胞因子，虽然它属于该超家族，但与现有家族没有很强的同源性，表明它是一个分歧成员，可能代表了这一组中新家族的第一个。单核细胞样细胞中MIC-1 mRNA的表达被多种与活化相关的刺激物上调，包括白细胞介素1 β，肿瘤坏死因子α MIC-1在CHO细胞中的表达导致前肽的蛋白水解裂解和M-r 25 kDa的富含半胱氨酸的二聚体蛋白的分泌，纯化的重组MIC-1能够抑制脂多糖诱导的巨噬细胞TNF-α产生，表明MIC-1在巨噬细胞中作为自分泌调节分子起作用。其响应于分泌的促炎细胞因子和TGF-β的产生可用于限制巨噬细胞活化的后期。
Macrophages play a key role in both normal and pathological processes involving immune and inflammatory responses, to a large extent through their capacity to secrete a wide range of biologically active molecules, To identify some of these as yet not characterized molecules, we have used a subtraction cloning approach designed to identify genes expressed in association with macrophage activation, One of these genes, designated macrophage inhibitory cytokine 1 (MIC-1), encodes a protein that bears the structural characteristics of a transforming growth factor beta (TGF-beta) superfamily cytokine, Although it belongs to this superfamily it has no strong homology to existing families, indicating that it is a divergent member that may represent the first of a new family within this grouping, Expression of MIC-1 mRNA in monocytoid cells is up-regulated by a variety of stimuli associated with activation, including interleukin 1 beta, tumor necrosis factor alpha (TNF-alpha), interleukin 2, and macrophage colony-stimulating factor but not interferon gamma, or lipopolysaccharide (LPS), Its expression is also increased by TGF-beta, Expression of MIC-1 in CHO cells results in the proteolytic cleavage of the propeptide and secretion of a cysteine-rich dimeric protein of M-r 25 kDa, Purified recombinant MIC-1 is able to inhibit lipopolysaccharide -induced macrophage TNF-alpha production, suggesting that MIC-1 acts in macrophages as an autocrine regulatory molecule, Its production in response to secreted proinflammatory cytokines and TGF-beta may serve to limit the later phases of macrophage activation.